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EC number: - | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
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- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Endpoint summary
Administrative data
Description of key information
One reliable animal study described in Haferkorn (2015) (modified OECD 429; method according to Ehlings et al. 2005; GLP compliant) is considered to be reliable without restrictions. The substance was determined not to be a skin sensitiser.
Skin sensitisation: not sensitising (modified OECD 429; GLP)
Key value for chemical safety assessment
Skin sensitisation
Link to relevant study records
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2015-06-12 to 2015-08-14
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
- Version / remarks:
- 2010-07-22
- Deviations:
- yes
- Remarks:
- modified OECD 429, method according to Ehlings et al. 2005
- Principles of method if other than guideline:
- The test was performed in accordance with the method according to Ehling et al (2005): An european inter-laboratory validation of alternative endpoints of the murine local lymph node assay: first round, Toxicology 212 (2005) 60-68 and Ehling et al (2005): An european inter-laboratory validation of alternative endpoints of the murine local lymph node assay: 2nd round, Toxicology 212 (2005) 69-79.
Threshold values of the stimulation indices of lymph node cell count (i.e. sensitising properties) and ear weight (i.e. irritating properties) were calculated by dividing the average values per group of the test item treated animals by the vehicle treated ones. Values above 1.4 (cell count) or 1.1 (ear weight) are considered positive
(these values were fixed empirically during the inter-laboratory validation of this method). In addition, the lymph node weights were determined for concentration related properties.. - GLP compliance:
- yes (incl. QA statement)
- Remarks:
- signed 2014-05-14
- Type of study:
- mouse local lymph node assay (LLNA)
- Specific details on test material used for the study:
- STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: kept dry in closed container at room temperature - Species:
- mouse
- Strain:
- NMRI
- Sex:
- female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age (on test day 1): 63 days
- Weight (on test day 1): 29 - 36 g
- Housing: animals were kept singly in MAKROLON cages (type III) with a basal surface of approx. 360 cm² and a height of approx. 14 cm. Granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages.
- Diet (ad libitum): commercial diet ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany); Food residue was removed.
- Water (ad libitum): tap water
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 55% ± 15% (maximum range)
- Air changes: 12 - 18/hour
- Photoperiod (hrs dark / hrs light): 12/12 - Vehicle:
- acetone/olive oil (4:1 v/v)
- Concentration:
- 10%, 25% and 50% (w/w) of spinels, cobalt tin grey
- No. of animals per dose:
- 6 female mice
- Details on study design:
- RANGE FINDING TESTS:
A preliminary experiment was carried out in 3 animals to examine the irritating potential and handling/application of the test item in order to select the appropriate concentrations. Three concentrations of 10, 25 and 50% of spinels, cobalt tin grey suspended in acetone/olive oil (4:1 v/v) were examined.
Spinels, cobalt tin grey was a blue powder. Hence, a 50% suspension was the highest feasible concentration of spinels, cobalt tin grey in acetone/olive oil (4:1 v/v).
The preliminary experiment was conducted under conditions identical to the main LLNA study, except there was no assessment of lymph node proliferation and only 1 animal per concentration was used. In this preliminary experiment no negative control was tested due to animal welfare reasons.
Both ears of each mouse were observed for erythema and scored using the scoring table (table 1) as shown in the field "Any other information on materials and methods incl. tables" below:
The results obtained were compared to reactions known from administration of recommended vehicles for example: acetone:olive oil (4:1, v/v) or dimethyl sulphoxide or other media used as vehicles in the LLNA (historical background data). For example, the erythema score for the vehicle acetone:olive oil (4:1) in NMRI mice is E: 0.
Results:
No irritating properties were observed in this preliminary experiment at concentrations of 10%, 25% or 50%, no differences in ear weight and ear thickness were noted.
MAIN STUDY
The experimental schedule of the assay was as follows:
Day 1:
The weight and any clinical observations of each animal were individually identified and recorded. In addition, ear swelling measurements were carried out at the helical edge of both ears using an Oditest micrometer.
Open application of 25 μL of the appropriate dilution of the test item, the vehicle alone or the positive control (as appropriate) were administered to the dorsum of each ear.
Days 2 and 3:
The application procedure carried out on day 1 was repeated.
On all administration days possible clinical signs were noted.
Day 4 (24 hours after the last application the animals were sacrificed under ether anaesthesia by cutting the aorta abdominalis):
Ear swelling measurements (immediately before sacrificing the mice) were carried out at the helical edge of both ears using an Oditest micrometer.
Punch biopsies of 8 mm in diameter of the apical area of both ears were prepared and immediately weighed on an analytical balance.
Lateral pairs of auricular lymph nodes draining the ear tissue were excised, carefully separated from remaining fatty tissue and weighed on an analytical balance immediately following preparation. The lymph nodes were then stored on ice in PBS/0.5% BSA and subjected to the preparation of single cell suspensions by mechanical tissue disaggregation. The cells were counted automatically in a cell counter.
OBSERVATIONS
- Clinical signs: animals were observed once daily for any clinical signs of local systemic irritation at the application site or of systemic toxicity. In addition, animals were checked regularly throughout the working day and on the weekend.
- Body weight: the weight of each mouse was recorded at the time of allocation of animals to groups (test day 1) and at the time of necropsy (test day 4).
ANALYSIS OF RESULTS
The so-called stimulation (or LLN-) indices to determine the sensitising potential were calculated by dividing the average absolute lymph node weight or lymph node cell counts per group of the test item treated animals by the vehicle treated ones.
Thus, in case of no stimulating effect the index for the lymph node cell count is always below 1.4 (cut-off value). An index above 1.4 is considered positive.
For lymph node weight significance at p ≤ 0.01 is considered positive (U-test according to MANN and WHITNEY). A possible concentration-response-relationship for the lymph node weight in order to determine a possible sensitising potential was examined by linear regression analysis employing PEARSON's correlation coefficient. U-test was performed for cell count, too. Outliers were determined according to the Nalimov test.
In addition, the acute inflammatory skin reaction (irritating potential) was measured by ear weight determination of circular biopsies of the ears and ear thickness measurements on test day 1 and test day 4 to identify skin irritation properties of the test item employing the U-test according to MANN and WHITNEY by comparing the test groups to the vehicle control.
The stimulation indices were calculated by dividing the average ear weight and average ear thickness on test day 4 per group of the test item treated animals by the vehicle treated ones. The cut-off threshold value for ear weight was set at 1.1. - Positive control substance(s):
- hexyl cinnamic aldehyde (CAS No 101-86-0)
- Statistics:
- Please refer to "details on study design"
- Positive control results:
- The positive control group caused the expected increases in lymph node cell count (SI: 1.474) and lymph node weight (statistically significant at p ≤ 0.01). Therefore, the study can be regarded as valid.
- Key result
- Parameter:
- SI
- Value:
- 1.012
- Test group / Remarks:
- 10 % (w/w) test item
- Remarks on result:
- other: 10 % (w/w) test item; lymph node cell count
- Key result
- Parameter:
- SI
- Value:
- 0.995
- Test group / Remarks:
- 10 % (w/w) test item
- Remarks on result:
- other: 10 % (w/w) test item; ear weight
- Key result
- Parameter:
- SI
- Value:
- 0.852
- Test group / Remarks:
- 25 % (w/w) test item
- Remarks on result:
- other: 25 % (w/w) test item; lymph node cell count
- Key result
- Parameter:
- SI
- Value:
- 0.984
- Test group / Remarks:
- 25 % (w/w) test item
- Remarks on result:
- other: 25 % (w/w) test item; ear weight
- Key result
- Parameter:
- SI
- Value:
- 0.882
- Test group / Remarks:
- 50 % (w/w) test item
- Remarks on result:
- other: 50 % (w/w) test item; lymph node cell count
- Key result
- Parameter:
- SI
- Value:
- 0.979
- Test group / Remarks:
- 50 % (w/w) test item
- Remarks on result:
- other: 50 % (w/w) test item; ear weight
- Cellular proliferation data / Observations:
- DETAILS ON STIMULATION INDEX CALCULATION
Threshold values of the stimulation indices of lymph node cell count and ear weight were calculated by dividing the average values per group of the test item treated animals by the vehicle treated ones. Values above 1.4 (cell count) or 1.1 (ear weight) are considered positive (these values were fixed empirically during the inter-laboratory validation of this method).
RESULTS ON SKIN SENSITISATION
In the main study treatment with spinels, cobalt tin grey at concentrations of 10%, 25% or 50% did not reveal any statistical significantly increased values for the lymph node cell count. The stimulation indices of the lymph node cell count did not exceed the threshold level of 1.4. In addition, no increase in the lymph node weight was observed. Hence, the test item is classified as not sensitising.
The threshold level for the ear weight of 1.1 was not exceeded and no increase of ear thickness was observed, i.e. no irritating properties were noted.
STIMULATION INDEX RESULTS OF LYMPH NODE WEIGHT AND EAR THICKNESS
10 % w/w: SI: 1.057 (lymph node weight); SI: 1.033 (ear thickness)
25 % w/w: SI: 1.075 (lymph node weight); SI: 1.000 (ear thickness)
50 % w/w: SI: 1.094 (lymph node weight); SI: 1.000 (ear thickness)
CLINICAL OBSERVATIONS:
No signs of local or systemic intolerance were recorded.
BODY WEIGHTS
The animal body weight was not affected by the treatment. - Interpretation of results:
- GHS criteria not met
- Conclusions:
- The substance is not a skin sensitiser.
According to Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does not require classification as skin sensitiser.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed (not sensitising)
- Additional information:
One reliable animal study described in Haferkorn (2015) (modified OECD 429; method according to Ehlings et al. 2005; GLP compliant) is considered to be reliable without restrictions. The substance was determined not to be a skin sensitiser.
Respiratory sensitisation
Endpoint conclusion
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Skin sensitisation
The substance does not possess a skin sensitisation potential and does not require classification as skin sensitiser according to Regulation (EC) No 1272/2008 and subsequent adaptations.
Respiratory sensitisation
During long-lasting industrial practice in the inorganic pigment industry, no cases of hypersensitivity have been observed until now by workers exposed directly to the substance. In contrast to bioavailable cobalt substance which are known to elicit sensitising properties, cobalt magnesium tin spinel is considered an inert, non-bioaccessible substance which has been tested negative for skin sensitisation (LLNA assay).
Assuming that both effects (skin and respiratory sensitisation) for cobalt are based on similar immunological mechanisms, the absence of skin sensitisation properties supports the assumption of an absence of respiratory sensitisation.
In conclusion, the classification criteria acc. to regulation (EC) 1272/2008 as respiratory sensitiser are not met for the pigment cobalt magnesium tin spinel
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